Endoplasmic reticulum localization of Sec12p is achieved by two mechanisms: Rer1p-dependent retrieval that requires the transmembrane domain and Rer1p-independent retention that involves the cytoplasmic domain

The analyses of signals are always complementary to the analyses of receptors. In the case of the KDEL/HDEL signal, Erd2p has been identified as its receptor (Semenza et al., 1990) . In the retrieval of membrane proteins with the dilysine motifs, the coatomer (COP I) binds to this signal and executes the Golgi-to-ER retrograde transport (Cosson and Letourneur et al., 1994) . What about the Sec12p signals? If the recognition of these signals is a receptor-mediated process, massive overproduction of the signals would give rise to saturation and overflow of the sorting mechanism. In the case of the authentic Sec12p, enormous overproduction does not lead to its missorting but rather complex phenomena including proliferation of the ER membrane, inhibition of ER-to-Golgi anterograde transport, and formation of the BiP bodies in the lumen of the ER (Nishikawa et al., 1994) . Such consequences are probably due to the imbalance of the Sarlp GTPase cycle caused by the increase of the catalytic sites of Sec12p as the guanine nucleotide exchange factor. Since the TMD of Sec12p does not have such an effect on Sarlp, we could test the effect of its overproduction. In fact, when the DSDm construct was expressed by the strong promoter of the glyceraldehyde-3-phosphate dehydrogenase gene on a multicopy plasmid, secretion of t~-factor was clearly observed, indicating that this chimeric protein was mislocalized to the late Golgi (M. Sato, unpublished data) . This suggests that the retrieval of Sec12p by the TMD signal is a saturable process, again implying the existence of a receptor.